Tislelizumab-Jsgr Plus Chemotherapy Receives FDA Approval for Advanced Esophageal Squamous Cell Carcinoma

Updated Tuesday, March 4, 2025, at 9:34 AM.

Tislelizumab-jsgr (Tevimbra; BeiGene, Ltd) in combination with a platinum-containing chemotherapy received FDA approval for first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥ 1). The decision is supported by significant improvements in overall survival benefit observed in the phase 3 RATIONALE-306 trial (NCT03783442).¹

Depiction of esophageal cancer | Image Credit: © kamonrat - stock.adobe.com

In 2040, there will likely be 957,000 new cases of esophageal cancer, an increase of over 60% from 2020, highlighting the need for more potent treatments. At the time of diagnosis, over two-thirds of patients have advanced or metastatic esophageal cancer, which is associated with a poorer prognosis and fatality. Patients with distant metastases are projected to have a 5-year survival rate of less than 6%. ESCC is the most prevalent histologic subtype of esophageal cancer, making up about 90% of all esophageal malignancies.²

Tislelizumab is a humanized immunoglobulin G4 PD-1 monoclonal antibody designed to have a high affinity and binding specificity for PD-1. It is intended to reduce binding to macrophages' Fc-gamma (Fcγ) receptors, assisting the body's immune cells in identifying and combating malignancies. As of March 2025, tislelizumab has FDA-approved indications for treatment of esophageal and gastric cancers.^2,3

In the randomized, placebo-controlled, double-blind, global, phase 3 RATIONALE-306 study, researchers evaluated the safety and efficacy of tislelizumab in combination with platinum-containing chemotherapy as a first-line treatment in adult patients with unresectable, locally advanced recurrent or metastatic ESCC. The trial involved a total of 649 patients who were randomized to receive either tislelizumab plus chemotherapy (n = 326) or placebo plus chemotherapy (n = 323). The primary end point was OS, which was met according to the final trial data.^1,2

Results in the subgroup of patients with PD-L1 greater than or equal to 1 were mostly responsible for the improvement in the intent-to-treat population, according to exploratory analyses. The median OS for patients in the tislelizumab plus chemotherapy group was 16.8 months, compared with 9.6 months for patients treated with placebo plus chemotherapy (HR: 0.66, [95% CI: 0.53, 0.82]), which resulted in a 34% lower risk of death in the PD-L1 positive (≥ 1) population (n = 481).²

The safety profile of tislelizumab plus chemotherapy was favorable, with the most frequent adverse effects (AEs) being (≥ 2) pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common (≥ 20%) AEs were anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.²

“The approval of [tislelizumab] in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease,” Nataliya Uboha, MD, associate professor, University of Wisconsin, Carbone Cancer Center, said in a press release. “There is a critical need for effective treatments of ESCC, and [tislelizumab] has been shown to improve outcomes in this patient population.”²

REFERENCES

1. A study of tislelizumab (BGB-A317) in combination with chemotherapy as first line treatment in participants with advanced esophageal squamous cell carcinoma. Updated October 26, 2024. Accessed March 4, 2025. https://clinicaltrials.gov/study/NCT03783442?term=NCT03783442&rank=1&tab=results

2. TEVIMBRA approved in U.S. for first-line treatment of advanced esophageal squamous cell carcinoma in combination with chemotherapy. BusinessWire. March 4, 2025. Accessed March 4, 2025.

3. Tevimbra FDA approval history. Drugs.com. December 30, 2024. Accessed March 4, 2025. https://www.drugs.com/history/tevimbra.html